Pub Date : 2026-02-01DOI: 10.1016/j.jtho.2025.12.103
{"title":"Tobacco News Update—From the IASLC Tobacco Control Committee","authors":"","doi":"10.1016/j.jtho.2025.12.103","DOIUrl":"10.1016/j.jtho.2025.12.103","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"21 2","pages":"Pages 211-214"},"PeriodicalIF":20.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtho.2025.10.009
Xiuning Le MD , Christina Baik MD , Byoung Chul Cho MD , Jonathan W. Riess MD , Zofia Piotrowska MD, MHS , Adrianus Johannes de Langen MD , Sarah B. Goldberg MD , Jonathan W. Goldman MD , Noemi Reguart MD , Yoshimasa Shiraishi MD , Helen Ambrose PhD , Paula G. Fraenkel MD , Brayan Merchan Ruiz MD , Paul E. Smith MSc , Kwan Ho Tang PhD , Helena A. Yu MD
Introduction
The ORCHARD (NCT03944772) study was conducted to characterize resistance mechanisms and identify optimal treatments after progressive disease (PD) on first-line osimertinib. We report results from the osimertinib plus savolitinib module.
Methods
Patients with EGFR-mutated NSCLC with PD on first-line osimertinib with MET gene amplification (≥4 copies of MET over tumor ploidy) per next-generation sequencing of a post-progression biopsy received osimertinib plus savolitinib. Primary end point was investigator-assessed objective response rate (ORR). Secondary end points included progression-free survival, duration of response, overall survival, and safety. Correlation of ORR with baseline molecular alterations was an exploratory analysis.
Results
A total of 32 patients were enrolled; all had tumors with MET amplification. At primary analysis cutoff (January 2023), confirmed ORR was 47% (80% confidence interval [CI]: 34–60). Median duration of response was 14.5 months (95% CI: 5.6–18.7). Median progression-free survival was 7.6 months (95% CI: 3.2–15.9). There was a trend toward increased ORR in patients with high MET gene copy number (≥10 versus <10). Furthermore, 14 patients (44%) had grade 3 or higher treatment-emergent adverse events; most often pneumonia (n = 3; 9%). At final database lock (May 2024), 20 patients (63%) had died; median overall survival was 20.7 months (95% CI: 9.9–34.8).
Conclusions
Osimertinib plus savolitinib demonstrated encouraging clinical benefit in patients with EGFR-mutated advanced NSCLC and MET amplification after PD on first-line osimertinib. Safety was consistent with profiles of the individual drugs.
{"title":"Osimertinib Plus Savolitinib in Patients With EGFR-Mutated Advanced NSCLC With MET Alterations After First-Line Osimertinib: Clinical Outcomes, Safety, and Biomarker Analysis: A Brief Report","authors":"Xiuning Le MD , Christina Baik MD , Byoung Chul Cho MD , Jonathan W. Riess MD , Zofia Piotrowska MD, MHS , Adrianus Johannes de Langen MD , Sarah B. Goldberg MD , Jonathan W. Goldman MD , Noemi Reguart MD , Yoshimasa Shiraishi MD , Helen Ambrose PhD , Paula G. Fraenkel MD , Brayan Merchan Ruiz MD , Paul E. Smith MSc , Kwan Ho Tang PhD , Helena A. Yu MD","doi":"10.1016/j.jtho.2025.10.009","DOIUrl":"10.1016/j.jtho.2025.10.009","url":null,"abstract":"<div><h3>Introduction</h3><div>The ORCHARD (NCT03944772) study was conducted to characterize resistance mechanisms and identify optimal treatments after progressive disease (PD) on first-line osimertinib. We report results from the osimertinib plus savolitinib module.</div></div><div><h3>Methods</h3><div>Patients with <em>EGFR</em>-mutated NSCLC with PD on first-line osimertinib with <em>MET</em> gene amplification (≥4 copies of <em>MET</em> over tumor ploidy) per next-generation sequencing of a post-progression biopsy received osimertinib plus savolitinib. Primary end point was investigator-assessed objective response rate (ORR). Secondary end points included progression-free survival, duration of response, overall survival, and safety. Correlation of ORR with baseline molecular alterations was an exploratory analysis.</div></div><div><h3>Results</h3><div>A total of 32 patients were enrolled; all had tumors with <em>MET</em> amplification. At primary analysis cutoff (January 2023), confirmed ORR was 47% (80% confidence interval [CI]: 34–60). Median duration of response was 14.5 months (95% CI: 5.6–18.7). Median progression-free survival was 7.6 months (95% CI: 3.2–15.9). There was a trend toward increased ORR in patients with high <em>MET</em> gene copy number (≥10 versus <10). Furthermore, 14 patients (44%) had grade 3 or higher treatment-emergent adverse events; most often pneumonia (n = 3; 9%). At final database lock (May 2024), 20 patients (63%) had died; median overall survival was 20.7 months (95% CI: 9.9–34.8).</div></div><div><h3>Conclusions</h3><div>Osimertinib plus savolitinib demonstrated encouraging clinical benefit in patients with <em>EGFR</em>-mutated advanced NSCLC and <em>MET</em> amplification after PD on first-line osimertinib. Safety was consistent with profiles of the individual drugs.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"21 2","pages":"Pages 318-327"},"PeriodicalIF":20.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtho.2025.11.017
Stephen Lam MD, FRCPC , David R. Baldwin MD, FRCP , Anand Devaraj MD , John Field PhD, FRCPath. , Claudia I. Henschke MD, PhD , Marjolein A. Heuvelmans MD, PhD , Rudolf M. Huber MD, PhD , Catherine Jones M.B.B.S., FRCR , Andrea Borondy-Kitts MS, MPH , Molly Siu Ching Li M.B.B.S., FHKAM , Renelle Myers MD, FRCPC , Raymond U. Osarogiagbon M.B.B.S., FACP , Hilary A. Robbins PhD , Martin C. Tammemägi DVM, MSc, PhD , Kathryn L. Taylor PhD , Natthaya Triphuridet MD, PhD , Randi M. Williams PhD, MPH , David Yankelevitz MD
In the past two decades, lung cancer screening (LCS) with low-dose computed tomography (LDCT) has emerged as one of the most effective strategies for reducing lung cancer mortality. Landmark trials, including NLST and NELSON, demonstrated mortality reductions exceeding 20%, establishing LDCT as the standard of care for early detection in high-risk populations. Currently, 13 countries have implemented national or regional LCS programs, with additional nations preparing for rollout. Advances in risk-prediction models, volumetric nodule assessment, and structured management protocols have improved precision and efficiency. Integration of artificial intelligence is enhancing nodule detection, prediction of malignancy risk, individualized screening intervals, and workflow optimization. Real-world evidence confirms improved stage distribution and suggests reduction in lung cancer mortality. Initiatives such as promoting community engagement, equitable access through geospatial mapping, and mobile screening will improve screening uptake and retention. Embedding tobacco dependence treatment within LCS further augments life-years gained. Complementary incidental pulmonary-nodule programs and expanding studies in people who have never smoked are extending the reach of early detection, whereas biomarker research is progressing toward integration with imaging-based screening. The potential to use LDCT scans to detect coronary heart disease and chronic obstructive pulmonary disease may have a major impact on future health care benefits. Ongoing efforts to harmonize data collection standards, establish quality indicators, and strengthen workforce training are essential to sustain high-quality implementation. As LCS evolves into a cornerstone of lung cancer control, continued innovation in risk stratification, imaging technologies, and biomarker integration will be key to maximizing global benefit and equity.
{"title":"A Game-Changing 20 Years: Progress and Future Directions in Lung Cancer Screening","authors":"Stephen Lam MD, FRCPC , David R. Baldwin MD, FRCP , Anand Devaraj MD , John Field PhD, FRCPath. , Claudia I. Henschke MD, PhD , Marjolein A. Heuvelmans MD, PhD , Rudolf M. Huber MD, PhD , Catherine Jones M.B.B.S., FRCR , Andrea Borondy-Kitts MS, MPH , Molly Siu Ching Li M.B.B.S., FHKAM , Renelle Myers MD, FRCPC , Raymond U. Osarogiagbon M.B.B.S., FACP , Hilary A. Robbins PhD , Martin C. Tammemägi DVM, MSc, PhD , Kathryn L. Taylor PhD , Natthaya Triphuridet MD, PhD , Randi M. Williams PhD, MPH , David Yankelevitz MD","doi":"10.1016/j.jtho.2025.11.017","DOIUrl":"10.1016/j.jtho.2025.11.017","url":null,"abstract":"<div><div>In the past two decades, lung cancer screening (LCS) with low-dose computed tomography (LDCT) has emerged as one of the most effective strategies for reducing lung cancer mortality. Landmark trials, including NLST and NELSON, demonstrated mortality reductions exceeding 20%, establishing LDCT as the standard of care for early detection in high-risk populations. Currently, 13 countries have implemented national or regional LCS programs, with additional nations preparing for rollout. Advances in risk-prediction models, volumetric nodule assessment, and structured management protocols have improved precision and efficiency. Integration of artificial intelligence is enhancing nodule detection, prediction of malignancy risk, individualized screening intervals, and workflow optimization. Real-world evidence confirms improved stage distribution and suggests reduction in lung cancer mortality. Initiatives such as promoting community engagement, equitable access through geospatial mapping, and mobile screening will improve screening uptake and retention. Embedding tobacco dependence treatment within LCS further augments life-years gained. Complementary incidental pulmonary-nodule programs and expanding studies in people who have never smoked are extending the reach of early detection, whereas biomarker research is progressing toward integration with imaging-based screening. The potential to use LDCT scans to detect coronary heart disease and chronic obstructive pulmonary disease may have a major impact on future health care benefits. Ongoing efforts to harmonize data collection standards, establish quality indicators, and strengthen workforce training are essential to sustain high-quality implementation. As LCS evolves into a cornerstone of lung cancer control, continued innovation in risk stratification, imaging technologies, and biomarker integration will be key to maximizing global benefit and equity.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"21 2","pages":"Pages 235-252"},"PeriodicalIF":20.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtho.2025.11.015
Wei-Chin Chang MD, PhD , Teh-Ying Chou MD, PhD
{"title":"Resolving the Staging Dilemma in Multiple Lung Cancers: A Prevalence-Weighted Bioinformatic Approach to the 2024 IASLC Recommendations","authors":"Wei-Chin Chang MD, PhD , Teh-Ying Chou MD, PhD","doi":"10.1016/j.jtho.2025.11.015","DOIUrl":"10.1016/j.jtho.2025.11.015","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"21 2","pages":"Pages 221-223"},"PeriodicalIF":20.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtho.2025.08.024
Hyungjin Kim MD, PhD , Eunseo Jo BA , Jinseob Kim MD , Seung Hun Jang MD, PhD , Joo Sung Sun MD , Gong Yong Jin MD, PhD , Hyae Young Kim MD, PhD , Yeol Kim MD, PhD , Jin Mo Goo MD, PhD
Introduction
Interval lung cancers (ILCs) are key indicators of lung cancer screening (LCS) performance. However, data on the proportion, characteristics, and mortality of ILCs under biennial screening in Asian populations remain limited.
Methods
We analyzed participants from the baseline biennial Korean national LCS program between 2019 and 2020. Screening-detected lung cancers (SLCs) were defined as those diagnosed within 1 year of a positive screening result. ILCs were defined as cancers diagnosed more than 1 year after a negative screening result but within 2 years or before the next screening. Risk factors for ILC were assessed using multivariable logistic regression among participants with a negative screening result. All-cause mortality was compared between SLCs and ILCs using multivariable Cox regression analysis.
Results
Among 124,595 participants, SLCs and ILCs occurred in 0.56% and 0.17%, respectively. ILCs accounted for 18.5% of all lung cancers within 2 years; 65.4% were in Lung-RADS category 1. Risk factors for ILC included older age (adjusted odds ratio [OR], 1.14; 95% confidence interval [CI]: 1.11–1.17; p < 0.001), greater smoking exposure (adjusted OR, 1.010; 95% CI: 1.004–1.016; p = 0.002), a history of malignancy (adjusted OR, 2.22; 95% CI: 1.41–3.51; p < 0.001), emphysema (adjusted OR, 2.88; 95% CI: 2.15–3.85; p < 0.001), and interstitial lung abnormalities (adjusted OR, 4.16; 95% CI: 2.88–6.01; p < 0.001). ILCs had higher all-cause mortality than SLCs (adjusted hazard ratio, 1.43; 95% CI: 1.13–1.80; p = 0.002).
Conclusions
ILCs are common under biennial LCS, making them potentially suboptimal for Asian heavy smokers.
{"title":"Screening-Detected Versus Interval Lung Cancer in the Biennial Korean National Lung Cancer Screening Program: Proportion, Characteristics, and Mortality","authors":"Hyungjin Kim MD, PhD , Eunseo Jo BA , Jinseob Kim MD , Seung Hun Jang MD, PhD , Joo Sung Sun MD , Gong Yong Jin MD, PhD , Hyae Young Kim MD, PhD , Yeol Kim MD, PhD , Jin Mo Goo MD, PhD","doi":"10.1016/j.jtho.2025.08.024","DOIUrl":"10.1016/j.jtho.2025.08.024","url":null,"abstract":"<div><h3>Introduction</h3><div>Interval lung cancers (ILCs) are key indicators of lung cancer screening (LCS) performance. However, data on the proportion, characteristics, and mortality of ILCs under biennial screening in Asian populations remain limited.</div></div><div><h3>Methods</h3><div>We analyzed participants from the baseline biennial Korean national LCS program between 2019 and 2020. Screening-detected lung cancers (SLCs) were defined as those diagnosed within 1 year of a positive screening result. ILCs were defined as cancers diagnosed more than 1 year after a negative screening result but within 2 years or before the next screening. Risk factors for ILC were assessed using multivariable logistic regression among participants with a negative screening result. All-cause mortality was compared between SLCs and ILCs using multivariable Cox regression analysis.</div></div><div><h3>Results</h3><div>Among 124,595 participants, SLCs and ILCs occurred in 0.56% and 0.17%, respectively. ILCs accounted for 18.5% of all lung cancers within 2 years; 65.4% were in Lung-RADS category 1. Risk factors for ILC included older age (adjusted odds ratio [OR], 1.14; 95% confidence interval [CI]: 1.11–1.17; <em>p</em> < 0.001), greater smoking exposure (adjusted OR, 1.010; 95% CI: 1.004–1.016; <em>p</em> = 0.002), a history of malignancy (adjusted OR, 2.22; 95% CI: 1.41–3.51; <em>p</em> < 0.001), emphysema (adjusted OR, 2.88; 95% CI: 2.15–3.85; <em>p</em> < 0.001), and interstitial lung abnormalities (adjusted OR, 4.16; 95% CI: 2.88–6.01; <em>p</em> < 0.001). ILCs had higher all-cause mortality than SLCs (adjusted hazard ratio, 1.43; 95% CI: 1.13–1.80; <em>p</em> = 0.002).</div></div><div><h3>Conclusions</h3><div>ILCs are common under biennial LCS, making them potentially suboptimal for Asian heavy smokers.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"21 2","pages":"Pages 283-293"},"PeriodicalIF":20.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtho.2025.10.010
Michael Allgäuer PhD , Klaus Kluck MS , Petros Christopoulos MD , Markus Ball PhD , Anna-Lena Volckmar PhD , Teodora Radonic MD, PhD , Lukas Bubendorf MD , Paul Hofman MD, PhD , Claus Peter Heußel MD , Hauke Winter MD , Felix Herth MD , Michael Thomas MD , Bauke Ylstra PhD , Solange Peters MD, PhD , Peter Schirmacher MD , Daniel Kazdal PhD , Jan Budczies PhD , Albrecht Stenzinger MD , Martina Kirchner PhD
Introduction
Accurate distinction between separate primary lung carcinomas (SPLCs) and intrapulmonary metastases (IPMs) is essential for staging and treatment of multifocal NSCLC. Next-generation sequencing (NGS) enables assessment of clonal relatedness. The proposed International Association for the Study of Lung Cancer (IASLC) algorithm integrates histologic and molecular data, though its clinical utility is yet to be validated.
Methods
We focused on the molecular component of the algorithm and assessed 240 tumor pairs from 120 patients with formalin-fixed, paraffin-embedded tumor samples that underwent small-scale gene-panel NGS testing (31–54 genes) within routine clinical care. Most tumors were adenocarcinomas (n = 222), with 18 tumors other NSCLC subtypes. Inconclusive pairs by molecular classification were subjected to large-scale panel analyses (531 genes). In addition, we developed a bioinformatic method to complement and refine the IASLC method.
Results
In total, 22 tumor pairs (18%) remained inconclusive and 16 (13%) were classified ambiguous (probable SPLCs) using the molecular IASLC method. Resequencing classified nine of 22 inconclusive pairs as IPMs. Using a newly developed bioinformatic method for clonality classification incorporating likelihood ratios of mutational prevalence and small-scale sequencing, only three pairs remained inconclusive (2%). Tumors classified as SPLCs had a significantly longer overall survival than IPMs.
Conclusions
Small-scale panel sequencing of biopsy material allows unambiguous clonality determination in three of four cases. Large-scale sequencing resolves approximately half of inconclusive cases. Our bioinformatic method reduces inconclusive pairs to 2% even with small-scale NGS. It is made publicly available as a Shiny App. Clonality is reflected in survival data and therefore pivotal in daily clinical practice.
{"title":"Advancing Lung Cancer Staging: Integrating IASLC Recommendations and Bioinformatics to Delineate Tumor Origins","authors":"Michael Allgäuer PhD , Klaus Kluck MS , Petros Christopoulos MD , Markus Ball PhD , Anna-Lena Volckmar PhD , Teodora Radonic MD, PhD , Lukas Bubendorf MD , Paul Hofman MD, PhD , Claus Peter Heußel MD , Hauke Winter MD , Felix Herth MD , Michael Thomas MD , Bauke Ylstra PhD , Solange Peters MD, PhD , Peter Schirmacher MD , Daniel Kazdal PhD , Jan Budczies PhD , Albrecht Stenzinger MD , Martina Kirchner PhD","doi":"10.1016/j.jtho.2025.10.010","DOIUrl":"10.1016/j.jtho.2025.10.010","url":null,"abstract":"<div><h3>Introduction</h3><div>Accurate distinction between separate primary lung carcinomas (SPLCs) and intrapulmonary metastases (IPMs) is essential for staging and treatment of multifocal NSCLC. Next-generation sequencing (NGS) enables assessment of clonal relatedness. The proposed International Association for the Study of Lung Cancer (IASLC) algorithm integrates histologic and molecular data, though its clinical utility is yet to be validated.</div></div><div><h3>Methods</h3><div>We focused on the molecular component of the algorithm and assessed 240 tumor pairs from 120 patients with formalin-fixed, paraffin-embedded tumor samples that underwent small-scale gene-panel NGS testing (31–54 genes) within routine clinical care. Most tumors were adenocarcinomas (n = 222), with 18 tumors other NSCLC subtypes. Inconclusive pairs by molecular classification were subjected to large-scale panel analyses (531 genes). In addition, we developed a bioinformatic method to complement and refine the IASLC method.</div></div><div><h3>Results</h3><div>In total, 22 tumor pairs (18%) remained inconclusive and 16 (13%) were classified ambiguous (probable SPLCs) using the molecular IASLC method. Resequencing classified nine of 22 inconclusive pairs as IPMs. Using a newly developed bioinformatic method for clonality classification incorporating likelihood ratios of mutational prevalence and small-scale sequencing, only three pairs remained inconclusive (2%). Tumors classified as SPLCs had a significantly longer overall survival than IPMs.</div></div><div><h3>Conclusions</h3><div>Small-scale panel sequencing of biopsy material allows unambiguous clonality determination in three of four cases. Large-scale sequencing resolves approximately half of inconclusive cases. Our bioinformatic method reduces inconclusive pairs to 2% even with small-scale NGS. It is made publicly available as a Shiny App. Clonality is reflected in survival data and therefore pivotal in daily clinical practice.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"21 2","pages":"Pages 267-282"},"PeriodicalIF":20.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145368302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtho.2025.11.007
Jan P. Van Meerbeeck MD, PhD , Jelle E. Bousema MD, PhD , Wen Wen MD , Paul E.Y. Van Schil MD, PhD
Accurate staging is pivotal in lung cancer management, yet standardized key performance indicators (KPIs) for staging practices are lacking. We identified a number of critical areas in the staging process and outlined a starter set of SMART KPIs for patients with early stage NSCLC. We propose clear definitions (numerators/denominators, timing anchors) and risk-adjusted benchmarks. These KPIs should be used to monitor and improve clinical practice; they are not intended to dictate the structure of the TNM classification, which must remain an objective, globally applicable anatomic language. Implementing staging KPIs can enhance diagnostic accuracy and treatment outcomes in lung cancer care.
{"title":"Staging of Lung Cancer: A Call for Developing Uniform and Universal Key Performance Indicators and Benchmarks to Elevate Clinical Standards","authors":"Jan P. Van Meerbeeck MD, PhD , Jelle E. Bousema MD, PhD , Wen Wen MD , Paul E.Y. Van Schil MD, PhD","doi":"10.1016/j.jtho.2025.11.007","DOIUrl":"10.1016/j.jtho.2025.11.007","url":null,"abstract":"<div><div>Accurate staging is pivotal in lung cancer management, yet standardized key performance indicators (KPIs) for staging practices are lacking. We identified a number of critical areas in the staging process and outlined a starter set of SMART KPIs for patients with early stage NSCLC. We propose clear definitions (numerators/denominators, timing anchors) and risk-adjusted benchmarks. These KPIs should be used to monitor and improve clinical practice; they are not intended to dictate the structure of the TNM classification, which must remain an objective, globally applicable anatomic language. Implementing staging KPIs can enhance diagnostic accuracy and treatment outcomes in lung cancer care.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"21 2","pages":"Pages 253-257"},"PeriodicalIF":20.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtho.2025.09.010
Federica Pecci MD , Prashasti Agrawal MD , Jessica S. Ross MD , Biagio Ricciuti MD, PhD , Seshiru Nakazawa MD, PhD , Alessandro Di Federico MD , Mihaela Aldea MD, PhD , Edoardo Garbo MD , Valentina Santo MD , Eleonora Gariazzo MD , Maisam Makarem MD, PhD , Danielle Haradon MS , Igor Odintsov MD , Marina Baine MD, PhD , William Travis MD , Soo-Ryum Yang MD , Paula A. Ugalde Figueroa MD , Katherine D. Gray MD , Mizuki Nishino MD, PhD , Maria Mayoral Penalva MD , Jamie E. Chaft MD
Introduction
MET exon 14 (METex14) skipping mutations are found in 3% to 4% of NSCLC and can be detected through DNA- or RNA-based sequencing assays. Although RNA sequencing simply reports skipping of exon 14, DNA sequencing assays indicate the precise DNA nucleotide changes that result in METex14 skipping. Here, we reveal the importance of DNA-based sequencing assays for identifying patients with multiple, distinct, METex14-mutant lung cancers.
Methods
NSCLC cases with available targeted exome next-generation sequencing through OncoPanel or Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assays were evaluated. Patients with METex14 mutations in ≥2 NSCLC tumor samples at any stage were reviewed to assess tumor relatedness based on clinicopathologic and genomic criteria.
Results
Among 589 patients with METex14-mutant NSCLC and available in-house next-generation sequencing, 112 had ≥2 NSCLC tumor samples sequenced with METex14 mutations; among these, seven patients had two distinct METex14-mutant primary lung cancers, and one patient had three primary METex14-mutant lung cancers. Four cases were synchronous primary cancers, occurring within 12 months of the initial diagnosis, whereas the other four were metachronous, occurring after 12 months. Comprehensive DNA genomic analysis confirmed the distinct clonality of the tumors, with each case showing different METex14 alterations and other distinct genomic events, supporting the diagnosis of independent primary lung cancers.
Conclusions
DNA-based sequencing of the MET gene improves staging accuracy to guide appropriate management for patients with multiple primary METex14-mutant NSCLCs.
{"title":"Brief Report: Critical Role for DNA-Based Sequencing in Discriminating Distinct Primary Lung Cancers With Different MET Exon 14 Skipping Mutations","authors":"Federica Pecci MD , Prashasti Agrawal MD , Jessica S. Ross MD , Biagio Ricciuti MD, PhD , Seshiru Nakazawa MD, PhD , Alessandro Di Federico MD , Mihaela Aldea MD, PhD , Edoardo Garbo MD , Valentina Santo MD , Eleonora Gariazzo MD , Maisam Makarem MD, PhD , Danielle Haradon MS , Igor Odintsov MD , Marina Baine MD, PhD , William Travis MD , Soo-Ryum Yang MD , Paula A. Ugalde Figueroa MD , Katherine D. Gray MD , Mizuki Nishino MD, PhD , Maria Mayoral Penalva MD , Jamie E. Chaft MD","doi":"10.1016/j.jtho.2025.09.010","DOIUrl":"10.1016/j.jtho.2025.09.010","url":null,"abstract":"<div><h3>Introduction</h3><div><em>MET</em> exon 14 (<em>MET</em>ex14) skipping mutations are found in 3% to 4% of NSCLC and can be detected through DNA- or RNA-based sequencing assays. Although RNA sequencing simply reports skipping of exon 14, DNA sequencing assays indicate the precise DNA nucleotide changes that result in <em>MET</em>ex14 skipping. Here, we reveal the importance of DNA-based sequencing assays for identifying patients with multiple, distinct, <em>MET</em>ex14-mutant lung cancers.</div></div><div><h3>Methods</h3><div>NSCLC cases with available targeted exome next-generation sequencing through OncoPanel or Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assays were evaluated. Patients with <em>MET</em>ex14 mutations in ≥2 NSCLC tumor samples at any stage were reviewed to assess tumor relatedness based on clinicopathologic and genomic criteria.</div></div><div><h3>Results</h3><div>Among 589 patients with <em>MET</em>ex14-mutant NSCLC and available in-house next-generation sequencing, 112 had ≥2 NSCLC tumor samples sequenced with <em>MET</em>ex14 mutations; among these, seven patients had two distinct <em>MET</em>ex14-mutant primary lung cancers, and one patient had three primary <em>MET</em>ex14-mutant lung cancers. Four cases were synchronous primary cancers, occurring within 12 months of the initial diagnosis, whereas the other four were metachronous, occurring after 12 months. Comprehensive DNA genomic analysis confirmed the distinct clonality of the tumors, with each case showing different <em>MET</em>ex14 alterations and other distinct genomic events, supporting the diagnosis of independent primary lung cancers.</div></div><div><h3>Conclusions</h3><div>DNA-based sequencing of the <em>MET</em> gene improves staging accuracy to guide appropriate management for patients with multiple primary <em>MET</em>ex14-mutant NSCLCs.</div></div>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"21 2","pages":"Pages 310-317"},"PeriodicalIF":20.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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